Noteworthy Chemistry

April 11, 2011

Aggregate formation enhances and blue-shifts light emission. Organic chromophores often aggregate into microscopic crystals. Strong fluorescence from such microcrystalline aggregates is uncommon because aggregation weakens and red-shifts light emission. Aggregation is therefore a challenge for scientists to create organic luminophores.

D. C. Neckers and coauthors at Bowling Green State University and the University of Cincinnati (both in OH) took up the challenge and developed a new luminogen that behaves oppositely to conventional luminophores and exhibits the novel phenomenon of aggregation-induced emission enhancement (AIEE).

The luminogen is trans-1-cyano-1,2-bis(4-carbazolylphenyl)ethylene (1). Whereas molecules of 1 dissolved in a “good” solvent (e.g., acetone) are weakly fluorescent, its aggregates suspended in a “poor” solvent (e.g., an acetone–water mixture) emit strongly. The emission of 1 is enhanced 16-fold and blue-shifted by 41 nm when it forms microcrystalline aggregates.

The researchers believe that the unusual AIEE effect is caused by strong supramolecular interactions in the microcrystalline aggregates that hold the luminogenic molecules in a rigid, twisted conformation. (Langmuir 2011, 27, 1573–1580; Ben Zhong Tang)

Functionalize polycarbonates by attaching azido groups. Interest in aliphatic polycarbonates for biomedical and environmental applications has increased because of their biocompatibility (or biodegradability) and low toxicity. Properties such as hydrophilicity, degradation rate, and mechanical characteristics of these polymers can be optimized by attaching pendant groups with varying functionalities.

X. Zhang, Z. Zhong*, and R. Zhuo* at Wuhan University (China) modified conventional aliphatic polycarbonates by using the ring-opening copolymerization of azido-functionalized trimethylene carbonate monomer 1 with 2,2-dimethyltrimethylene carbonate (2). 1,6-Hexanediol is the initiator for the polymer-forming reaction, which is carried out in bulk without solvent; Oct is octyl.

Monomer 1 is prepared by cyclizing an azido diol with ethyl chloroformate. The resulting azido-substituted copolymer 3 provides a convenient scaffold for functionalization with propargyl derivatives, which leads to polymer 4 via the 1,3-dipolar click cyclization reaction. The authors demonstrated the efficiency of the click reaction by quantitatively grafting the poly(ethylene glycol) (PEG) substituent onto the copolymer with no side reactions on the main polymer chain.

The polymer variant with a polycarbonate main chain and PEG side chains is amphiphilic. The authors demonstrated the formation of ≈100-nm–diam micelles by self-assembly in selected solvents. Considering the biocompatibility and biodegradability of the micelle’s amphiphilic structure, they suggest that the micelle particles might be used as carriers for drug delivery. (Macromolecules 2011, 44, Article ASAP DOI: 1755–1759; W. Jerry Patterson)

STEM-in-SEM beats TEM for polymer characterization. Transmission electron microscopy (TEM) is a valuable technique for characterizing polymer morphology. The microstructure of a sample can be imaged with very high resolution. But this method has drawbacks: It is clumsy for analyzing the entire sample, images are best shown on the nanometer scale, specimens must be specially prepared, and the high-voltage beam may damage polymer structures.

Scanning transmission electron microscopy in the scanning electron microscope (STEM-in-SEM) is a new tool for polymer characterization. It combines the advantages of scanning and transmission microscopy: the low voltage used in STEM and the high-resolution images of SEM. O. Guise*, C. Strom, and N. Preschilla at SABIC Innovative Plastics (Selkirk, NY) and Reliance Industries (Navi Mumbai, India) compared STEM-in-SEM with TEM for demonstrating polymer morphology.

Sample preparation is not demanding, and specimen size can range from the <1 μm to millimeters. Like TEM, STEM-in-SEM can show phase separations in immiscible polymer blends. The dispersion and distribution of up to three components are shown clearly. Electron-beam–sensitive polymer composites, which are damaged by TEM, are preserved in STEM-in-SEM. An auto-sampler can be installed as a time-saving option; it allows consecutive analysis of multiple samples. (Polymer 2011, 52, 1278–1285; Sally Peng Li)

Functionalize quinone C–H bonds directly with boronic acids. Quinones are “privileged” structures in medicinal chemistry because of their electron- and proton-transfer properties in living organisms. These properties, however, hinder traditional organic reactions, such as Heck coupling, when quinones are used as substrates. Other protocols for modifying quinones usually require prehalogenation or free-radical conditions.

P. S. Baran and co-workers at the Scripps Research Institute (La Jolla, CA) used the inherent reactivity of quinones to functionalize their C–H bonds with boronic acids. The reaction is catalyzed by AgNO3, and persulfate is used as a co-oxidant. This reaction requires no expensive reagents, proceeds at room temperature, and uses a two-phase H2O–CH2Cl2 solvent system. The reaction tolerates many boronic acid alkylating and arylating agents; exceptions are very electron-poor or hindered boronic acids. The reaction stops at monoarylation of the quinone.

The CH2Cl2 solvent can be replaced by environmentally benign α,α,α-trifluorotoluene, and the reaction can be performed in an open vessel at ambient temperature. In a scaled-up procedure, the organic solvent can be omitted without lowering the yield. Using this method, the authors prepared adducts of benzoquinone with the biologically active molecules estrone and farnesol in 51 and 58% yield, respectively. (J. Am. Chem. Soc. 2011, 133, 3292–3295, JosÉ C. Barros)

Block copolymer–homopolymer blends enhance ordering. W. H. Jo, S. H. Kim, and coauthors at Inha University (Incheon, Korea) and Seoul National University report a processing and assembly method for well-ordered poly(2-hexylthiophene)-b-poly(methyl methacrylate) (P3HT-b-PMMA) copolymers that uses a blending technique. Whereas P3HT-b-PMMMA thin films assembled with slow solvent vapor annealing exhibit intermediate ordering, adding higher molecular weight P3HT or lower molecular weight PMMA homopolymers (≈10 wt%) produces a self-assembled lamellar morphology with significant long-range ordering in the absence of annealing.

Higher homopolymer contents result in macrophase separation of the blends. PMMA is a better promoter of the highly ordered microstructure, which is a complex function of system parameters. The well-ordered fibrillar morphology is maintained after UV etching of the PMMA domains. The P3HT in P3HT-b-PMMA–10 wt% PMMA blends maintains the edge-on orientation and ordering needed for photovoltaic applications.

Photoluminescence is significantly quenched in mixtures of P3HT-b-PMMA–10 wt% PMMA and the electron acceptor [6,6]-phenyl-C61-butyric acid methyl ester (PCBM), suggesting templated distribution of the PCBM in a highly ordered morphology. The authors also report high field-effect mobility, which scales with the degree of ordering. (Macromolecules 2011, 44, Article ASAP DOI: 1771-1774; LaShanda Korley)

A 1,3 γ-silyl elimination forms perfluoroalkylbicyclobutanes. Wiberg’s 1963 preparation of [1.1.0]bicyclobutane showed that an unusually highly strained bicyclic ring system can be formed (Wiberg, K. B.; Lampmann, G. M. Tetrahedron Lett. 1963, 4, 2173–2175). Many bicyclobutane derivatives have been prepared since then, but perfluoromethyl derivatives remain elusive—probably because of the likely elimination of fluoride under anionic conditions.

L. J. Tilley and co-workers at Stonehill College (Easton, MA) report a synthesis of perfluoroalkyl derivatives such as 1 that uses cationic bridgehead bond formation techniques. Their preparation of the trifluoromethyl derivative is shown in the figure. A key feature of the method is the formation of a trimethylsilyl-substituted cyclobutane intermediate in which the electron-withdrawing perfluoroalkyl group at the incipient cationic center enhances neighboring γ-silyl group participation.

The synthesis starts with a [2 + 2] cyclization of vinyltrichlorisilane (2) with dichloroketene (formed in situ from Cl3COCl) to give cyclobutanone derivative 3. Subsequent dehalogenation of 3 gives cyclobutanone 4. The authors used the Prakash method for trifluoromethylating 4; the alcohol functionality also forms to give 5 stereoselectively. The alcohol is protected as p-toluenesulfonate 6, which readily undergoes solvolysis under mild conditions to give target structure 1. The pentafluoroethyl analogue is formed with the same method.

The ease of converting 6 to 1 emphasizes the capability of the trifluoromethyl group to enhance 1,3 C–C bond formation via the γ-silyl effect. The authors suggest that increased electron demand at the cationic center induced by the electron-withdrawing trifluoromethyl group increases participation of the silyl group. They believe that this method offers a potential route to a variety of highly strained, high-energy bridgehead polycyclic hydrocarbons. They also suggest extending the method to prepare trifluoromethylcyclopropanes. (Org. Lett. 2011, 13, Article ASAP DOI: 1646-1649; W. Jerry Patterson)

Detect trace protein aggregates with luminescent nanoparticles. Protein aggregation is the underlying cause of neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s. Detecting and characterizing aggregation is essential for developing rational treatments. Normally, high concentrations of protein solution are required and the analysis is time-consuming. S. Pihlasalo and co-workers at the University of Turku (Finland) developed a time-resolved luminescence resonance energy transfer (TR-LRET) method to determine trace amounts of protein aggregation that uses luminescent polymer nanoparticles.

The authors used Eu(III)-doped polystyrene nanoparticles as energy donors. Unaggregated protein molecules, such as γ-globulin, bind on the nanoparticle surfaces by electrostatic attraction (1). The bound molecules prevent proteins labeled with the fluorescent energy acceptor Alexa Fluor 680 (Molecular Probes, Eugene, OR) from absorbing on the Eu(III) surface. Therefore, these complexes emit little fluorescence when they are irradiated at 340 nm.

The authors heated isolated protein molecules to form aggregates and then labeled them with the fluorescent dye. The modified aggregates occupy less of the Eu(III) surface (2), so when the particles are irradiated, the fluorophore absorbs light and transfers energy to Eu(III). Blue fluorescent emission is observed at 730 nm. This TR-LRET method can detect picomolar concentrations of labeled γ-globulin aggregates. (Anal. Chem. 2011, 83, 1163–1166; Sally Peng Li)

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